The present invention relates to improved processes for preparing oxindoles and related amide containing compounds, and to useful intermediates thereof.
Several complicated routes to preparing 2-oxindoles are known in the art and include reaction of isatins with hydrazine (D. S. Soriano, J. Chem. Edu., 1992, 70:332 and Crestini, Synth. Commun., 1994, 24:2835). The Soriano route entails the use of expensive anhydrous ethanol as the solvent during the process and a tedious purification process, thereby making the process unfavorable to scale up. The Crestini route utilizes explosive pure hydrazine. Both methods require high temperatures (about 200° C.) and the yields are only moderate.
Another method of preparing 2-oxindoles utilizes a weak base such as sodium acetate as the catalyst, but the process includes boiling off a high boiling point solvent such as dimethylformamide (DMF), which is not practical in a large-scale synthesis (U.S. Pat. No. 5,973,165 and Japanese Patent Publication No. 2000239253).
A further route utilizes a catalyst such as diazabicyclooctane, diazabicycloundecene, ethyldiisopropylamine, or combinations thereof as the catalyst, but the yields are only moderate and the purification is complicated (Schwendinger et al., International Patent Publication No. 2001047884).
What is needed in the art are alternative processes for preparing 2-oxindoles that provide inexpensive reagents, high yields, and simple purifications, especially on a large scale.